Background: In South Africa, nurses are the largest category of the health care providers. Their optimal performance is critical for the successful implementation of impending health sector reforms. Objective: This paper examines the occurrence of agency nursing, moonlighting, and overtime among nurses in South Africa, and the factors influencing moonlighting. Design: This cross-sectional survey was a one-stage cluster random sample of 80 hospitals in four South African provinces, selected with stratification from the public and private health sectors. On the survey day, all nurses working in critical care, theatre, emergency, maternity, and general medical and surgical wards completed a self-administered questionnaire after giving informed consent. In addition to demographic information, the questionnaire elicited information on the frequency of agency nursing, moonlighting, and overtime, and the nurses’ reasons for doing moonlighting. Survey data were weighted and analysed using STATA version 12. Results: The majority of survey participants (n=3,784) were South African (98.0%), female (92.7%), and employed in government (52.8%). Their mean age was 41.5 years (SD 10.4). The occurrence of moonlighting among nurses in the 12 months preceding the survey was 28.0% [95% CI: 24.2–32.1], the frequency of agency nursing was 37.8% [95% CI: 32.4–43.6], while 56.0% of nurses did overtime [95% CI: 51.4–60.4]. In the multiple logistic regression analysis, predictors of moonlighting were province, sector of primary employment, unit of work, category of nurse, and having children. The odds of moonlighting was 1.51 [95% CI: 1.03–2.21] times higher for private sector nurses than for public nurses, while the odds ratio for auxiliary nurses was 0.61 [95% CI: 0.47–0.79] compared to professional nurses. The odds of moonlighting was 1.49 [95% CI: 1.18–1.89] for nurses with children, compared to those without. Conclusions: Agency nursing, moonlighting, and overtime are common among South African nurses, but have received insufficient policy attention. These issues need to be addressed as part of the implementation of comprehensive health workforce strategies.